Anti-galectin-9 antibodies and uses thereof

Abstract

Disclosed herein are methods for identifying a subject as having certain solid cancers such as breast cancer, colorectal colon cancer, or non-small cell lung cancer, or being at risk for the cancer based on the level of Galectin-9 in a biological sample (e.g., a blood sample) from a subject suspected of having the solid cancer.

1 .- 60 . (canceled) 
     
     
         61 . A method for identifying a human cancer patient and treating the human cancer patient, the method comprising:
 (i) providing a biological sample of a subject suspected of having a cancer,   (ii) measuring the level of galectin-9 in the biological sample,   (iii) identifying the subject as having the cancer or being at risk for the cancer based on the level of galectin-9 in the biological sample, wherein an elevated level of galectin-9 in the biological sample of the subject relative to a predetermined reference level indicates that the subject has the cancer or is at risk for the cancer and wherein the cancer is breast cancer, colorectal colon cancer (CRC), pancreatic cancer, or non-small cell lung cancer (NSCLC), and   (iv) administering to the subject an effective amount of an anti-Galectin-9 antibody, wherein the anti-Galectin-9 antibody comprises a light chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 1, a light chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 2, and a light chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 3 and comprises a heavy chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 4, a heavy chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 5, and a heavy chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 6.   
     
     
         62 . The method of  claim 61 , wherein the biological sample is a blood sample. 
     
     
         63 . The method of  claim 62 , wherein the blood sample is a serum sample or a plasma sample. 
     
     
         64 . The method of  claim 62 , wherein the level of galectin-9 is measured by an immunoassay. 
     
     
         65 . The method of  claim 61 , wherein the method further comprises determining tumor burden of the subject or cancer patient based on the level of galectin-9 in the biological sample. 
     
     
         66 . The method of  claim 61 , wherein the method further comprises determining metastatic status of the cancer in the subject based on the level of galectin-9 in the biological sample. 
     
     
         67 . The method of  claim 61 , wherein the cancer is pancreatic cancer. 
     
     
         68 . The method of  claim 67 , wherein the pancreatic cancer is pancreatic ductal adenocarcinoma (PDA). 
     
     
         69 . The method of  claim 61 , wherein the method further comprises: performing one or more additional diagnostic assays to confirm occurrence of the cancer or tumor burden of the cancer. 
     
     
         70 . The method of  claim 61 , wherein the anti-Galectin-9 antibody comprises a light chain variable domain of SEQ ID NO: 8, and a heavy chain variable domain of SEQ ID NO: 7. 
     
     
         71 . The method of  claim 70 , wherein the anti-Galectin-9 antibody is an IgG1 or IgG4 molecule. 
     
     
         72 . The method of  claim 71 , wherein the anti-Galectin-9 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:19 and a light chain comprising the amino acid sequence of SEQ ID NO:15. 
     
     
         73 . The method of  claim 61 , further comprising administering to the subject an effective amount of an anti-cancer therapy comprising a checkpoint inhibitor. 
     
     
         74 . The method of  claim 73 , wherein the checkpoint inhibitor is an anti-PD-1 antibody or an anti-PD-L1 antibody. 
     
     
         75 . The method of  claim 74 , wherein the anti-PD1 antibody is selected from the group consisting of pembrolizumab, nivolumab, tislelizumab or cemiplimab. 
     
     
         76 . The method of  claim 74 , wherein the anti-PD1 antibody is tislelizumab. 
     
     
         77 . A method of treating a human subject having a solid tumor comprising:
 (i) providing a biological sample of a subject having a cancer,   (ii) measuring the level of galectin-9 in the biological sample,   (iii) identifying the subject as having the cancer based on the level of galectin-9 in the biological sample, wherein an elevated level of galectin-9 in the biological sample of the subject relative to a predetermined reference level indicates that the subject has the cancer, and wherein the cancer is breast cancer, colorectal colon cancer (CRC), pancreatic cancer, or non-small cell lung cancer (NSCLC), and   (iv) administering to the subject a therapeutically effective amount an anti-Galectin-9 antibody, wherein the anti-Galectin-9 antibody comprises a light chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 1, a light chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 2, and a light chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 3 and comprises a heavy chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 4, a heavy chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 5, and a heavy chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 6.   
     
     
         78 . The method of  claim 77 , wherein the biological sample is a blood sample. 
     
     
         79 . The method of  claim 78 , wherein the blood sample is a serum sample or a plasma sample. 
     
     
         80 . The method of  claim 79 , wherein the level of galectin-9 is measured by an immunoassay. 
     
     
         81 . The method of  claim 80 , wherein the method further comprises determining tumor burden of the subject or cancer patient based on the level of galectin-9 in the biological sample. 
     
     
         82 . The method of  claim 77 , wherein the method further comprises determining metastatic status of the cancer in the subject based on the level of galectin-9 in the biological sample. 
     
     
         83 . The method of  claim 77 , wherein the cancer is pancreatic cancer. 
     
     
         84 . The method of  claim 83 , wherein the pancreatic cancer is pancreatic ductal adenocarcinoma (PDA). 
     
     
         85 . The method of  claim 77 , wherein the method further comprises: performing one or more additional diagnostic assays to confirm occurrence of the cancer or tumor burden of the cancer. 
     
     
         86 . The method of  claim 77 , wherein the anti-Galectin-9 antibody comprises a light chain variable domain of SEQ ID NO: 8, and a heavy chain variable domain of SEQ ID NO: 7. 
     
     
         87 . The method of  claim 86 , wherein the anti-Galectin-9 antibody is an IgG1 or IgG4 molecule. 
     
     
         88 . The method of  claim 87 , wherein the anti-Galectin-9 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:19 and a light chain comprising the amino acid sequence of SEQ ID NO:15. 
     
     
         89 . The method of  claim 77 , further comprising administering to the subject an effective amount of an anti-cancer therapy comprising a checkpoint inhibitor. 
     
     
         90 . The method of  claim 89 , wherein the checkpoint inhibitor is an anti-PD-1 antibody or an anti-PD-L1 antibody. 
     
     
         91 . The method of  claim 90 , wherein the anti-PD1 antibody is selected from the group consisting of pembrolizumab, nivolumab, tislelizumab or cemiplimab. 
     
     
         92 . The method of  claim 91 , wherein the anti-PD1 antibody is tislelizumab.